U.S. Pat. No. 2,099,402, issued Nov. 16, 1937 to J. W. Keller describes a pill or tablet designed for delivery of a combination of drugs to animals. According to the '402 patent, the pill or tablet is made containing a desired dose of the drug or drugs, the action of which is desired to come last. Over this pill or tablet, an enteric coating of proper thickness and appropriate composition is applied, followed by a second coat which consists of the dose of the second drug or drugs. Over all this, if desired, a suitable finishing coat may be placed.
U.S. Pat. No. 2,853,420, issued Sept. 23, 1958 to H. Lowey describes ethyl cellulose coatings for shaped medicinal preparations. The '420 patent provides for a medically active shaped preparation, containing a number of substantially round medically inactive granulated carriers, each having an impregnation of a solution of therapeutically active material in ethyl cellulose. Upon the impregnation a number of action-delaying ethyl cellulose coatings are present, the number of coatings on at least some of the carriers being different from the number of coatings on the remaining carriers by at least 25. Each of the coatings is substantially not thicker than 0.1% of the radius of the carrier, and 25 coatings contain a total amount of coating material of the order of 1% of the weight of the inactive carrier.
U.S. Pat. No. 2,928,770, issued Mar. 15, 1960 to F. M. Bardani describes a sustained action pill. The sustained action pill of Bardani is formed of layers of medicament separated by control coatings. Each coating includes a porous membrane, initially having a substance closing its pores, to control the flow of alimentary fluids therethrough to the medicament. The time each coating withstands the fluids before becoming porous and the rate of flow of fluids through the coating is determined by its composition and the manner in which it is formed on the medicament layers. Upon subjection of the sustained action pill to alimentary fluids, the material closing the pores is gradually removed and fluids moving through the resultant permeable membrane leach medicament therethrough. Before one medicament layer is dissolved, the next coating is wetted by the fluids to initiate opening of its pores.
U.S. Pat. No. 2,953,497, issued Sept. 20, 1960 to H. A. Press, relates to shaped medicinal preparations, such as tablets, comprising particles or granules of two or more kinds having different dispersion times in the system of the patient to which the preparation is administered. According to the '497 patent, granules consisting, for example, of sugar and cornstarch and granulated with corn syrup are prepared in a coating pan with the application of heat. The therapeutically active ingredients are used in the form of solutions containing a minimum amount of solvent, which are introduced into the uncoated granules or are applied to the granules between the first and last coatings thereof with shellac or cellulose acetate phthalate. A batch of granules is divided into two or more portions which are then treated separately by coating and/or impregnation with different solutions of a binder. The granule portions, having different binder coatings, are combined and compressed to the desired shape and weight, after being mixed with a solid diluent for protecting granules from being crushed during compression.
U.S. Pat. No. 2,996,431, issued Aug. 15, 1961 to R. H. Barry, relates to pharmaceutical tablets which can be disintegrated into a mass of small-size particles by the pressure of the thumb on the tablet and against a table or other surface in a single operation without danger of injury. Barry found that an otherwise crush-resistant tablet can be made friable under thumb pressure by incorporating therein a certain quantity of small pellets of more or less rounded shapes, such as spheroid, ellipsoid, and ovoid forms.
U.S. Pat. No. 3,115,441, issued Dec. 24, 1963 to V. M. Hermelin, relates to timed release pharmaceutical preparations in tablet form, comprising a plurality of finely divided hard particles of a drug, each particle being individually coated with a permeable solution-resistant coating, the particles being dispersed throughout a compressed matrix consisting predominantly of the same drug. In use, the tablet per se disintegrates almost immediately and the initial dosage comprising the matrix is absorbed. The hard particles, however, resist disintegration for about three hours, after which the drug begins to leach out at a steady, attenuated rate which offsets the rate at which the drug disappears from the system.
U.S. Pat. No. 3,119,742, issued Jan. 28, 1964 to K. R. Heimlich and D. R. MacDonnell, relates to a method of making high dosage sustained release pharmaceutical pellets. In the method of Heimlich and MacDonnell, crystals of medicaments are coating with additional medicament to produce smooth, spherical pellets which are divided into a plurality of groups, each of which groups is coated with a slowly digestible or dispersable time delay coating to provide pellets of a diameter from about 0.1 to about 2.0 millimeters, containing from 85 to 95% active medicament and providing different times of release of the medicament on ingestion. The resulting pellets are combined in standard gelatin capsules.
U.S. Pat. No. 3,906,086, issued Sept. 16, 1975 to Guy et al. relates to a timed release aspirin composition. The composition of the '086 patent is made by coating particles of aspirin prior to tableting with a coating solution containing cellulose acetate phthalate. The tablet so produced remains substantially intact while in the stomach and dissolves at a slow, controlled rate in the intestinal tract. Aspirin tablets providing both immediate pain relief and timed release are produced by pressing separate layers of aspirin particles coated in this manner and ordinary uncoated aspirin into a double-layered tablet.
U.S. Pat. No. 4,025,613, issued May 24, 1977, also to Guy et al., is a divisional of the same application.
U.S. Pat. No. 4,173,626, issued Nov. 6, 1979 to Dempski et al. relates to a sustained release indomethacin composition. In the product of the '626 patent, a pellet formulation encapsulated in a hard gelatin capsule is used. A portion of the pellets is uncoated for immediate and rapid release of indomethacin for elevating the plasma level. The remainder of the pellets are coated with a polymer to sustain the plasma level. The uncoated and coated pellets may be mixed with nonmedicated pellets as a capsule filler.
U.S. Pat. No. 4,250,166, issued Feb. 10, 1981 to Maekawa et al. relates to a long-acting cefalexin preparation. The preparation involves a portion of enteric coated cefalexin administered concurrently with a plain, quick releasing cefalexin. The coated preparation is preferably coated in particle form, and when administered orally, exists in a particle form in the stomach. Preferably, the coating layer is made from a coating material having a dissolution pH of from 5.5 to 6.5.
European Patent No. 63,266, filed Mar. 31, 1982 and based on a German priority document dated Apr. 7, 1981 relates to long-acting preparations for maintenance therapy with the calcium antagonist gallopamil and verapamil. The compositions are standard and contain a fast-release fraction and a slow-release fraction.